PROJECT SUMMARY/ABSTRACT This revised project is designed to investigate a new safe, non-radioactive HP 13C mpMRI exam approach for creating a metabolic imaging solution for the unmet clinical need of detecting aggressive prostate cancer in patients prior to enrollment or on ?Active Surveillance? with correlations to ?gold standard? MR/US fusion- guided biopsy findings, and other clinical measures including current imaging parameters. This project was designed to fit the goals of PAR-16-089 Imaging and Biomarkers for Early detection of Aggressive Cancer that states: ?The specific objective of this FOA is to stimulate and support cancer imaging and biomarker research to develop, optimize, and clinically validate novel methods? to address the ??unmet clinical need to more accurately identify early-stage aggressive cancers and distinguish lesions that are life threatening from those that are not?. In response to the prior critique, we have significantly modified this study application following the reviewers' suggestions and addressing their concerns. The clinicians on our multidisciplinary team designed this revised study based on their unmet need to identify which untreated prostate cancer patients (thousands per year) have only low risk disease and can be managed by Active Surveillance (AS) and which have aggressive cancer, missed on biopsy, but still organ-confined and should be treated. Molecular imaging with FDG- or PSMA-PET is used for detecting metastatic disease, but high uptake in the bladder and normal prostatic tissues hinders the critical detection of high-grade cancer within the prostate. Based on strong preliminary preclinical & patient data showing a significant correlation of elevated HP 13C-pyruvate to 13C-lactate conversion in high grade prostate cancer, our clinical team created this study design testing improved, safe, lower-cost HP 13C MR molecular imaging techniques as a 5min addition to a standard-of-care mpMRI exam with correlations to subsequent MR/US fusion-guided biopsy findings; ?gold- standard? for this patient population. We aim to study patients (N=110) referred for mpMRI either to rule out missed aggressive disease at biopsy diagnosis prior to deciding on AS or as a consequence of a rising PSA while on AS. Also a subset (N=44) of these patients that enter AS, will be followed yearly with HP+mpMRI exams followed by MR/US fusion-guided biopsies in order to determine if a significant increase in kPL of any intra-prostatic lesion is an early predictor of disease progression (Gleason score upgrading). The success of this project could have exceptional clinical impact including: 1) Increased confidence that those entering AS do not have aggressive prostate cancer; 2) Early detection of aggressive cancer in AS patients; and 3) Improved guidance of biopsy and subsequent treatment of metabolically aggressive organ-confined cancer.